sébastien r. goudreau

+catalyst

R I Ar Ar

X X

X

Sébastien R. Goudreau

Literature Meeting

Diaryliodonium Salts in Coupling Diaryliodonium Salts in Coupling ReactionsReactions

November 9th, 2009

2

LPd

LPdX

RLPd

Nu

R

Nu EE X

R XNu R

oxidativeaddition

reductiveelimination

substitution

N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457-2483.

Cross-Coupling: General MechanismCross-Coupling: General Mechanism

Oxidative AdditionFavored by Electron-Rich Palladiumand Electron-Poor R group

Substitution (trans-metalation)Favored by Electron-Poor Palladiumand Electron-Rich Nu group

3

I

X

LPd

LPdX

RLPd

Nu

R

Nu EE X

R XNu R

oxidativeaddition


substitution

Cross-Coupling: General MechanismCross-Coupling: General Mechanism

X = I > OTf > Br >>> Cl

diaryliodonium salts


106 faster then X = I

4P. J. Stang, V. V. Zhdankin, Chem. Rev. 1996, 96, 1123-1178. E. A. Merritt, B. Olofsson, Angew. Chem., Int. Ed. 2009, ASAP

ReactivityReactivity

5

I

X

NuI

X

NuM

M

I Nu

I

X

I

X MM I XM

+

P. J. Stang, V. V. Zhdankin, Chem. Rev. 1996, 96, 1123-1178. E. A. Merritt, B. Olofsson, Angew. Chem., Int. Ed. 2009, ASAP

ReactivityReactivity

6P. J. Stang, V. V. Zhdankin, Chem. Rev. 1996, 96, 1123-1178. E. A. Merritt, B. Olofsson, Angew. Chem., Int. Ed. 2009, ASAP

NucleophilesNucleophiles

7

Cross-Cross-CouplingCoupling

8

(Ph3P)2PdX

R

(Ph3P)2PdNu

R

Nu B

R XNu R

oxidativeaddition


substitution

Pd(PPh3)4

-2PPh3

Pd(PPh3)2

OH

OR2

OH

R2O B OH

OR2

OH

(Ph3P)2PdOR2

R

Nu BOH

OH

MOR2

M

M

MOR2

MX

B(OH)2 + I

Pd(PPh3)4

MOR2

X Y X Y

Suzuki Cross-Coupling ReactionSuzuki Cross-Coupling Reaction


9

B(OH)2 + I

Pd(PPh3)4

DME, 80 °C

54%

aq. K2CO3

HO

HO

H

HO

+

39%

Ph B(OH)2 + I NO2 Ph NO2

Pd(PPh3)4 : 8h, 23%

acetone, 65 °C

85%

aq. K2CO3

Pd(OAc)2 : 45 min, 98%



Ph B(OH)2 +Br

O

Ph

OPd(PPh3)4

DME, 100 °C

CsF

85%

10


S.-K. Kang, H.-W. Lee, S.-B. Jang, P.-S. Ho, J. Org. Chem. 1996, 61, 4720-4724.

Ph B(OH)2 + [Ph2I]BF4

High yield without Base !

11

(Ph3P)2PdPh

(Ph3P)2PdNu

Ph

Nu B

Nu Ph

oxidativeaddition


substitution

Pd(PPh3)4

-2PPh3

Pd(PPh3)2

OH

OR2

OH

R2O B OH

OR2

OH

(Ph3P)2PdOR2

Ph

Nu BOH

OH

MOR2

M

M

MOR2

MBF4

[Ph2I]BF4

PhI

BF4



12



(Ph3P)2PdPh

(Ph3P)2PdNu

Ph

Nu Ph

oxidativeaddition


substitution

Pd(PPh3)4

-2PPh3

Pd(PPh3)2

BOH

OHNu B

OH

OH

[Ph2I]BF4

PhI

BF4

BF4O

B

Nu

OH

H+

BHO OH

OB

Nu

OHH+ Nu2

13

Method A: Pd(PPh3)4 (0.2 mol %)

Method B: Pd(OAc)2 (0.2 mol %)

Ar B(OH)2 + RAr[R2I]BF4Na2CO3

DME/H2O (4:1)



14

S.-K. Kang, T. Yamaguchi, T.-H. Kim, P.-S. Ho, J. Org. Chem. 1996, 61, 9082-9083.

Copper-Catalyzed “Suzuki-Type” ReactionCopper-Catalyzed “Suzuki-Type” Reaction

Reaction did not work with ArI

Boronic acids

15

ICuPh

ICuNu

Ph

Nu B

Nu Ph

oxidativeaddition


substitution

CuI

OH

OR2

OH

R2O B OH

OR2

OH

ICuOR2

Ph

Nu BOH

OH

MOR2

M

M

MOR2

MBF4

[Ph2I]BF4

PhI

BF4

Copper-Catalyzed “Suzuki-Type” ReactionCopper-Catalyzed “Suzuki-Type” Reaction


16

Carbonylative Copper-Catalyzed “Suzuki-Type” ReactionCarbonylative Copper-Catalyzed “Suzuki-Type” Reaction


S.-K. Kang, S.-W. Lee, M.-S. Kim, H.-S. Kwon, Synth. Commun. 2001, 31, 1721 - 1725.S.-K. Kang, H.-C. Ryu, J.-W. Kim, Synth. Commun. 2001, 31, 1021 - 1026.

J.-M. Becht, C. L. Drian, Org. Lett. 2008, 10, 3161-3164.

Diaryliodonium salts work in all cross coupling reactions !

17



(Ph3P)2PdPh

(Ph3P)2PdNu

Ph

Nu Ph

oxidativeaddition


substitution

Pd(PPh3)4

-2PPh3

Pd(PPh3)2

BOH

OHNu B

OH

OH

[Ph2I]BF4

PhI

BF4

BF4O

B

Nu

OH

H+

BHO OH

OB

Nu

OHH+ Nu2

Fast oxydative addition

Electrophilic Palladium(II)

18

Pd Catalyzed C-H Pd Catalyzed C-H FunctionalizationFunctionalization

19

O. Daugulis, V. G. Zaitsev, Angew. Chem., Int. Ed. 2005, 44, 4046-4048.

+catalyst

H Ar Ar

Y Y

X


cyclo-palladation

ZR H

Z(AcO)2Pd

R H

ZPdRAcO

II

Pd(OAc)2

II

AcOH

ZPdRX

IV

R2

OAc

ZRR2

oxidativeaddition

R2X

AcOH

HX +

ZPd

R H II


cyclo-palladation

ZPdRAcO

II

ZRR2

oxidativeaddition

LnPdAr

PdLn

OAcAr

HX

AcOH+

OAc

ZR H

R X

AcOH

Cyclopalladation MechanismsCyclopalladation Mechanisms

20


+catalyst

H Ar Ar

Y Y

X

(Ph3P)2PdX

R

R X

oxidativeaddition


Pd(PPh3)4

-2PPh3

Pd(PPh3)2

electrophilicpalladation

(Ph3P)2PdR

H

X

(Ph3P)2PdR

R


Pd(OAc)2


AcOPd H

AcO

AcOPd

R

AcOH

oxidativeaddition

PdRPh

IV

X

OAc

R X

AcOH

HX +

Electrophilic Palladation MechanismsElectrophilic Palladation Mechanisms

21



cyclo-palladation

Pd(OAc)2

AcOH

oxidativeaddition

O

tBuHN

H

OHN

tBuOAc

OAcH

OHN

tBuOAc

AcOH

OHN

tBu Ar

OAc

[Ar2I]PF6

IVPF6

O

tBuHN

ArHPF6 +


cyclo-palladation

oxidativeaddition

R2X

LnPdAr

[Ar2I]PF6PdLn

HPF6

AcOH+

OAc

PhI +

OHN

tBuAr

OAcH

O

tBuHN

OHN

tBuAr

O

tBuHN

Ar+

ZaitsevZaitsev

22


ZaitsevZaitsev

23


Reaction faster with Ar-I containing electron-donating groups

Reaction is faster with anilides containing electron-donating groups

ZaitsevZaitsev

24


Pd(OAc)2


R

AcOH

oxidativeaddition

AcOH

+

[Ar2I]PF6

HPF6

PhI

PdAcO

NH

tBuOL

HN tBu

O

PdAcO H

AcO

NH

tBuOL

OHN

tBu Ar

OAc

IVPF6

LnPdAr

oxidativeaddition


PdLn


PdR H

X

R[Ar2I]PF6

PF6

HN tBu

O

NH

tBuOL

PdR

NH

tBuOL

HN

O

tBu

Mechanism ?Mechanism ?


25

D. Kalyani, N. R. Deprez, L. V. Desai, M. S. Sanford, J. Am. Chem. Soc. 2005, 127, 7330-7331.

Substrate [Ph2I]BF4

(1.1-2.5 equiv)+

Pd(OAc)2 (5 mol %)

AcOH, benzene100 °C, 8-24 h

Product

SanfordSanford

26


SanfordSanford

Substrate [Ph2I]BF4

(1.1-2.5 equiv)+

Pd(OAc)2 (5 mol %)

AcOH, benzene100 °C, 8-24 h

Product

27


(1.1-1.3 equiv)

+Pd(OAc)2 (5 mol %)

100 °C, 12 hN AcOH

I ArN

Ar

SanfordSanford

28


(1.1-1.3 equiv)

+Pd(OAc)2 (5 mol %)

100 °C, 12 hN AcOH

I ArN

Ar

Reaction does not work with Ph-I or PhOTf


cyclo-palladation

Pd(OAc)2

AcOH

oxidativeaddition

O

tBuHN

H

OHN

tBuOAc

OAcH

OHN

tBuOAc

AcOH

OHN

tBu Ar

OAc

[Ar2I]PF6

IVPF6

O

tBuHN

ArHPF6 +



Pd(OAc)2


R

AcOH

oxidativeaddition

AcOH

+

[Ar2I]PF6

HPF6

PhI

PdAcO

NH

tBuOL

HN tBu

O

PdAcO H

AcO

NH

tBuOL

OHN

tBu Ar

OAc

IVPF6

29



cyclo-palladation

Pd(OAc)2

AcOH

oxidativeaddition

O

tBuHN

H

OHN

tBuOAc

OAcH

OHN

tBuOAc

AcOH

OHN

tBu Ar

OAc

[Ar2I]PF6

IVPF6

O

tBuHN

ArHPF6 +



Pd(OAc)2


R

AcOH

oxidativeaddition

AcOH

+

[Ar2I]PF6

HPF6

PhI

PdAcO

NH

tBuOL

HN tBu

O

PdAcO H

AcO

NH

tBuOL

OHN

tBu Ar

OAc

IVPF6

30

N. R. Deprez, D. Kalyani, A. Krause, M. S. Sanford, J. Am. Chem. Soc. 2006, 128, 4972-4973.

SanfordSanford

31


SanfordSanford

32

SanfordSanford


33

D. C. Powers, M. A. L. Geibel, J. E. M. N. Klein, T. Ritter, J. Am. Chem. Soc. 2009, ASAP.

RitterRitter

34

RitterRitter

D. C. Powers, M. A. L. Geibel, J. E. M. N. Klein, T. Ritter, J. Am. Chem. Soc. 2009, ASAP.

35

Cu Catalyzed C-H Cu Catalyzed C-H FunctionalizationFunctionalization

36

R. J. Phipps, N. P. Grimster, M. J. Gaunt, J. Am. Chem. Soc. 2008, 130, 8172-8174.

GauntGaunt

37


GauntGaunt

38


GauntGaunt

39


GauntGaunt

40


GauntGaunt

41


GauntGaunt

42

R. J. Phipps, M. J. Gaunt, Science 2009, 323, 1593-1597.

GauntGaunt

43

R. J. Phipps, M. J. Gaunt, Science 2009, 323, 1593-1597.

GauntGaunt

44

GauntGaunt

45

SynthesisSynthesis

46

M. Bielawski, B. Olofsson, Chem. Commun. 2007, 2521-2523.

SynthesisSynthesis

M. Bielawski, M. Zhu, B. Olofsson, Adv. Synth. Catal. 2007, 349, 2610-2618.

47

M. Bielawski, B. Olofsson, Chem. Commun. 2007, 2521-2523.

SynthesisSynthesis

M. Bielawski, M. Zhu, B. Olofsson, Adv. Synth. Catal. 2007, 349, 2610-2618.

48

SynthesisSynthesis

M. Zhu, N. Jalalian, B. Olofsson, Synlett 2008, 592-596.E. A. Merritt, J. Malmgren, F. J. Klinke, B. Olofsson, Synlett 2009, 2009, 2277-2280.

49

ConclusionConclusion

+catalyst

R I Ar Ar

X X

X

Diaryliodonium salts:

Cross-Coupling

Pd Catalyzed C-H Functionalization

Pd Catalyzed C-H Functionalization

Synthesis

50

ThanksThanks

sébastien r. goudreau

Documents

cross coupling reactions

coupling reactionsnovember

diaryliodonium salts

general mechanismx

cyclopalladation mechanismso

otf br cldiaryliodonium

high yield